There is a fundamental gap in our understanding of the functional significance that periodic input has on cen- tral olfactory representations. Our long-term goal is to understand the neural basis of odor encoding and how this process in turn affects perception and behavior. The objective of this application is to characterize how the dynamics of periodic input affect olfactory perception and identify the physiological mechanisms responsible for optimizing olfactory responses. Our central hypothesis is that olfactory systems have evolved to respond optimally to periodic rather than continuous stimulation and that this ability is mediated by local antennal lobe processing and centrifugal input that is related to the generation of wing movement. The rationale underlying the research is that, once we understand how periodic input enhances primary olfactory function, we will be better able to characterize central representations and their relationship to perception. Furthermore, these data will provide new insights into the fundamental heuristics through which better artificial olfactory sensors can be implemented for diagnostic use in human health and safety. The proposed re- search is therefore relevant to that part of NIH's mission that pertains to the acquisition of "fundamental knowledge about the nature and behavior of living systems and the application of that knowledge" particularly with respect to diagnosis and prevention of human diseases. Guided by strong preliminary data, this hypothesis will be tested in two specific aims: 1) Determine the characteristics of periodic stimulation that optimize the neurobehavior basis of odor processing and acuity;and 2) Investigate cellular mechanisms that enhance neural and behavioral responses to pulsed sensory input. The Aim 1 working hypothesis is the dynamics of airflow around the antennae induced by the wing beat cycle affect the neural representations in a way that enhances olfactory acuity as measured psychophysically. The working hypothesis for Aim 2 is that the interaction of local synaptic activity in antennal lobe work in conjunction with input from other brain regions to actively gate input. The results of the proposed research are innovative because they elucidate how input and primary processing of olfactory stimuli are affected by periodic input and how resulting changes in neural representation affect sensory perception. Furthermore we establish the mechanisms that mediate the neurophysiological basis of discrete pulse tracking behavior and establish how disruption of these mechanisms, in turn affects olfactory acuity. The proposed research is significant because central olfactory processing, as well as attempts to replicate this process artificially, are both dependent on the initial interaction of the sensory array with the environment. The results of this work will provide new insights into: 1) the universality of periodic input;2) the temporal constraints input places on odor processing;3) whether multiple olfactory samples are necessary and are integrated;4) the consequences of deviating from normal olfactory sampling;5) the mechanisms for gating input signals;and 6) ongoing efforts to design better olfactory based sensors. PUBLIC HEALTH RELEVANCE: The proposed studies are an important yet understudied area of olfaction that has the potential of elucidating optimal stimulus parameters for odor detection and discrimination and the physiological mechanisms that underlie this optimization. The proposed research has direct relevance to public health because they will establish parameters by which biological systems optimize odor signal processing;this in turn will aid design of artificial detector designs. Such detectors are used for diagnosis of human disease and detection of hazardous chemical traces in the environment as a disease prevention measure.